USPTO Patents Application 09589288

Application No. 09/589,288

Reply to Examiner Interview Summary

AMENDMENTS TO THE CLAIMS

This listing of claims replaces all prior versions, and listings, of claims in the
application.

1.-194, (Cancelled)

195. (Previously Presented) A method of inhibiting B lymphocytes comprising
administering an effective amount of an antibody that binds a protein whose amino acid
sequence is

MDDSTEREQS RLTSCLKKRE EMKLKECVSI LPRKESPSVR SSKDGKLLAA
TLLLALLSCC LTVVSFYQVA ALQGDLASLR AELQGHHAEK LPAGAGAPKA
GLEEAPAVTA GLKIFEPPAP GEGNSSQNSR NKRAVQGPEE TVTQDCLQLI
ADSETPTIQK GSYTFVPWLL SFKRGSALEE KENKILVKET GYFFIYGQVL
YTDKTYAMGH LIQRKKVHVF GDELSLVTLF RCIQNMPETL PNNSCYSAGI
AKLEEGDELQ LAIPRENAQI SLDGDVTFFG ALKLL (SEQ ID NO:2)
wherein B lymphocytes are inhibited,

196. (Previously Presented) A method of inhibiting B lymphocyte proliferation
comprising administering an effective amount of an antibody that binds Neutrokine-alpha
(SEQ ID NO:2), wherein B lymphocyte proliferation is inhibited,

197. (Previously Presented) A method of inhibiting B lymphocyte differentiation
comprising administering an effective amount of an antibody that binds Neutrokine-alpha
(SEQ ID NO:2), wherein B lymphocyte differentiation is inhibited.

198. (Previously Presented) The method of any one of claims 195-197, wherein the
antibody is a monoclonal antibody.

199. (Previously Presented) The method of any one of claims 195-197, wherein the
antibody is recombinantly produced.

200. (Previously Presented) The method of any one of claims 195-197, wherein the
antibody is a chimeric antibody.

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201. (Previously Presented) The method of any one of claims 195-197, wherein the
antibody is a humanized antibody.

202. (Previously Presented) The method of any one of claims 195-1 97, wherein the
antibody comprises human constant domains.

203. (Previously Presented) The method of any one of claims 195-197, wherein the
antibody is a F(ab')2 fragment.

204. (Previously Presented) The method of any one of claims 195-197, wherein the
antibody is a polyclonal antibody.

205. (Previously Presented) The method of any one of claims 195-197, wherein the
antibody is a Fab fragment.

206. (Previously Presented) The method of any one of claims 195-197, wherein the
antibody is administered to an individual.

207. (Previously Presented) The method of any one of claims 195-197, wherein the
antibody is administered to a cell culture.

208. -221. (Cancelled)

222. (Previously Presented) A method of treating an autoimmune disease or
disorder comprising administering to an individual, an effective amount of an antagonistic
antibody or portion thereof that specifically binds a protein consisting of the amino acid
sequence of amino acid residues 134-285 of SEQ ID NO:2.

223. (Previously Presented) The method of claim 222 wherein the antibody or
portion thereof is a monoclonal antibody.

224. (Previously Presented) The method of claim 222 wherein the antibody or
portion thereof is a polyclonal antibody.

225. (Previously Presented) The method of claim 222 wherein the antibody or
portion thereof is a Fab fragment.

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226. (Previously Presented) The method of claim 222 wherein the antibody or
portion thereof is labeled.

227. (Previously Presented) The method of claim 226 wherein the label is selected
from the group consisting of:

(a) an enzyme label;

(b) a radioisotope;

(c) a fluorescent label; and

(d) biotin.

228, (Previously Presented) The method of claim 227 wherein the label is a
radioisotope selected from the group consisting of:

(a) '^^l;
(b)

(c) ^^'l;

(d) "2ln;and

(e) ^'^'"Tc.

229. (Previously Presented) A method of treating rheumatoid arthritis comprising
administering to an individual, an effective amount of an antagonistic antibody or portion
thereof that specifically binds a protein consisting of the amino acid sequence of amino acid
residues 134-285 of SEQ ID NO:2.

230, (Previously Presented) The method of claim 229 wherein the antibody or
portion thereof is a monoclonal antibody.

23 1 , (Previously Presented) The method of claim 229 wherein the antibody or
portion thereof is a polyclonal antibody.

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232. (Previously Presented) The method of claim 229 wherein the antibody or
portion thereof is a Fab fragment.

233. (Previously Presented) The method of claim 229 wherein the antibody or
portion thereof is labeled.

234. (Previously Presented) The method of claim 233 wherein the label is selected
from the group consisting of:

(a) an enzyme label;

(b) a radioisotope;

(c) a fluorescent label; and

(d) biotin.

235. (Previously Presented) The method of claim 234 wherein the label is a
radioisotope selected from the group consisting of:

(a) '^^l;

(b) '^'i;

(c) '^'i;

(d) "^In;and

(e) ''^'"Tc.

236. (Previously Presented) A method of inhibiting B lymphocyte proliferation,
differentiation or survival comprising administering to an individual or a cell culture
containing B lymphocytes, an effective amount of an antagonistic antibody or portion thereof
that specifically binds a protein consisting of an amino acid sequence selected from the group
consisting of:

(a) the amino acid sequence of amino acid residues n to 285 of SEQ ID NO:2,
where n is an integer in the range of 2-190;

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(b) the amino acid sequence of amino acid residues 1 to m of SEQ ID NO:2,
where m is an integer in the range of 274 to 284; and

(c) the amino acid sequence of amino acid residues n to m of SEQ ID NO:2,
where n is an integer in the range of 2-190 and m is an integer in the range of 274-284.

237. (Previously Presented) The method of claim 236 wherein the protein consists
of amino acid sequence (a).

238. (Previously Presented) The method of claim 236 wherein the protein consists
of amino acid sequence (b).

239. (Previously Presented) The method of claim 236 wherein the protein consists
of amino acid sequence (c).

240. (Previously Presented) The method of claim 236 wherein the antibody or
portion thereof is a monoclonal antibody.

241 . (Previously Presented) The method of claim 236 wherein the antibody or
portion thereof is a polyclonal antibody.

242. (Previously Presented) The method of claim 236 wherein the antibody or
portion thereof is a Fab fragment.

243. (Previously Presented) The method of claim 236 wherein the antibody or
portion thereof is labeled.

244. (Previously Presented) The method of claim 243 wherein the label is selected
from the group consisting of:

(a)

an enzyme label;

(b)

a radioisotope;

(c)

a fluorescent label; and

(d)

biotin.

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245. (Previously Presented) The method of claim 244 wherein the label is a
radioisotope selected from the group consisting of:

(a) ^^^i;

(b) ^^^i;

(c) ^^^i;

(d) ^^^In;and

(e) ^^^^Tc.

246. (Previously Presented) A method of inhibiting B lymphocyte proliferation,
differentiation, or survival comprising administering to an individual or a cell culture
containing B lymphocytes, an effective amount of an antagonistic antibody or portion thereof
that specifically binds a protein consisting of the amino acid sequence of amino acid residues
134-285 of SEQ ID NO:2.

247. (Previously Presented) The method of claim 246 wherein the antibody or
portion thereof is a monoclonal antibody.

248. (Previously Presented) The method of claim 246 wherein the antibody or
portion thereof is a polyclonal antibody.

249. (Previously Presented) The method of claim 246 wherein the antibody or
portion thereof is a Fab fragment.

250. (Previously Presented) The method of claim 246 wherein the antibody or
portion thereof is labeled.

251 . (Previously Presented) The method of claim 250 wherein the label is selected
from the group consisting of:

(a) an enzyme label;

(b) a radioisotope;

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(c) a fluorescent label; and

(d) biotin.

252. (Previously Presented) The method of claim 251 wherein the label is a
radioisotope selected from the group consisting of:

(a) ^^^i;

(b) ^^^i;

(c) ^^^i;

(d) ^^^In; and

(e) ^^^"Tc.

253. (Previously Presented) The method of claim 222 wherein the autoimmune
disease or disorder is systemic lupus erythematosus.

254. (Previously Presented) A method of treating an autoimmune disease or
disorder comprising administering to an individual, an effective amount of an antagonistic
antibody or portion thereof that specifically binds to an isolated recombinant Neutrokine-a
protein purified from a cell culture wherein the cells in said cell culture comprise a
polynucleotide encoding amino acids 1-285 of SEQ ID NO:2 operably associated with a
regulatory sequence that controls gene expression.

255. (Previously Presented) The method of claim 254 wherein the antibody or
portion thereof is a monoclonal antibody.

256. (Previously Presented) The method of claim 254 wherein the antibody or
portion thereof is a polyclonal antibody.

257. (Previously Presented) The method of claim 254 wherein the antibody or
portion thereof is a Fab fragment.

258. (Previously Presented) The method of claim 254 wherein the antibody or
portion thereof is labeled.

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259. (Previously Presented) The method of claim 258 wherein the label is selected
from the group consisting of:

(a) an enzyme label;

(b) a radioisotope;

(c) a fluorescent label; and

(d) biotin.

(Previously Presented) The method of claim 259 wherein the label is a
selected from the group consisting of:

125t.

261 . (Previously Presented) The method of claim 254 wherein the autoimmune
disease or disorder is systemic lupus erythematosus.

262. (Previously Presented) A method of treating rheumatoid arthritis comprising
administering to an individual, an effective amount of an antagonistic antibody or portion
thereof that specifically binds to an isolated recombinant Neutrokine-a protein purified from
a cell culture wherein the cells in said cell culture comprise a polynucleotide encoding amino
acids 1-285 of SEQ ID NO:2 operably associated with a regulatory sequence that controls
gene expression.

263. (Previously Presented) The method of claim 262 wherein the antibody or
portion thereof is a monoclonal antibody.

260.
radioisotope

(a)

(b)

(c)

(d)

(e)

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264. (Previously Presented) The method of claim 262 w^herein the antibody or
portion thereof is a polyclonal antibody.

265. (Previously Presented) The method of claim 262 wherein the antibody or
portion thereof is a Fab fragment.

266. (Previously Presented) The method of claim 262 wherein the antibody or
portion thereof is labeled.

267. (Previously Presented) The method of claim 266 wherein the label is selected
from the group consisting of:

(a) an enzyme label;

(b) a radioisotope;

(c) a fluorescent label; and

(d) biotin.

268. (Previously Presented) The method of claim 267 wherein the label is a
radioisotope selected from the group consisting of:

(a) '^^i;

(b) '^'i;

(c) '^'i;

(d) "^In;and

(e) ^^""Tc.

269. (Previously Presented) The method of claim 236 which comprises
administering to an individual an effective amount of said antagonistic antibody or portion
thereof.

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270. (Previously Presented) The method of claim 236 which comprises
administering to a cell culture containing B lymphocytes an effective amount of said
antagonistic antibody or portion thereof.

271. (Previously Presented) The method of claim 246 which comprises
administering to an individual an effective amount of said antagonistic antibody or portion
thereof.

272. (Previously Presented) The method of claim 246 which comprises
administering to a cell culture containing B lymphocytes an effective amount of said
antagonistic antibody or portion thereof.

273. (Previously Presented) The method of claim 222 wherein said antibody or
portion thereof is administered intravenously.

274. (Previously Presented) The method of claim 222 which comprises
administering between 0.1 and 20 mg/kg of the patient's body weight of said antibody or
portion thereof.

275. (Previously Presented) The method of claim 229 wherein said antibody or
portion thereof is administered intravenously.

276. (Previously Presented) The method of claim 229 which comprises
administering between 0.1 and 20 mg/kg of the patient's body weight of said antibody or
portion thereof.

277. (Previously Presented) The method of claim 254 wherein said antibody or
portion thereof is administered intravenously.

278. (Previously Presented) The method of claim 254 which comprises
administering between 0.1 and 20 mg/kg of the patienfs body weight of said antibody or
portion thereof.

279. (Previously Presented) The method of claim 262 wherein said antibody or
portion thereof is administered intravenously.

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280. (Previously Presented) The method of claim 262 which comprises
administering between 0. 1 and 20 mg/kg of the patient's body weight of said antibody or
portion thereof

281 . (Previously Presented) The method of claim 222, wherein the autoimmune
disease or disorder is selected from the group consisting of systemic lupus erythematosus,
idiopathic thrombocytopoietic purpura (ITP), Sjogren's syndrome, Waldenstrom's
macroglobulinaemia, multiple sclerosis, cancer, asthma, nephritis, diabetes, scleroderma,
vasculitis, cryoglobulinaemia, graft-versus-host disease (GVHD), renal transplantation, and
antiphospholipid syndrome.

282. (Previously Presented) The method of claim 28 1 , wherein the antibody or
portion thereof is a monoclonal antibody.

283. (Previously Presented) The method of claim 281, wherein the antibody or
portion thereof is a polyclonal antibody.

284. (Previously Presented) The method of claim 281, wherein the antibody or
portion thereof is a Fab fragment.

285. (Previously Presented) The method of claim 281, wherein the antibody or
portion thereof is labeled,

286. (Previously Presented) The method of claim 285, wherein the label is selected
from the group consisting of:

(a) an enzyme label;

(b) a radioisotope;

(c) a fluorescent label; and

(d) biotin.

287. (Previously Presented) The method of claim 286, wherein the label is a
radioisotope selected from the group consisting of:

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(a)

125

(b)

121

I;

(c)

131

(d) ^^^In;and

(e) ^^^"Tc.

288. (Previously Presented) The method of claim 254, wherein the autoimmune
disease or disorder is selected from the group consisting of systemic lupus erythematosus,
idiopathic thrombocytopoietic purpura (ITP), Sjogren's syndrome, Waldenstrom's
macroglobulinaemia, multiple sclerosis, cancer, asthma, nephritis, diabetes, scleroderma,
vasculitis, cryoglobulinaemia, graft-versus-host disease (GVHD), renal transplantation, and
antiphospholipid syndrome.

289. (Previously Presented) The method of claim 281, wherein the antibody or
portion thereof is administered intravenously.

290. (Previously Presented) The method of claim 28 1 , wherein the method
comprises administering between 0.1 and 20 mg/kg of the patient's body weight of the
antibody or portion thereof.

29 1 . (Previously Presented) The method of claim 281, wherein the autoimmune
disease or disorder is idiopathic thrombocytopietic purpura (ITP).

292. (Previously Presented) The method of claim 28 1 , wherein the autoimmune
disease or disorder is Sjogren's syndrome.

293. (Previously Presented) The method of claim 281 , wherein the autoimmune
disease or disorder is multiple sclerosis.

294. (Previously Presented) The method of claim 281 , wherein the autoimmune
disease or disorder is renal transplantation.

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295. (Previously Presented) The method of claim 288, wherein the autoimmune
disease or disorder is systemic lupus erythematosus.

296. (Canceled)

297. (Previously Presented) The method of claim 288, wherein the autoimmune
disease or disorder is idiopathic thrombocytopietic purpura (ITP).

298. (Previously Presented) The method of claim 288, wherein the autoimmune
disease or disorder is Sjogren's syndrome.

299. (Previously Presented) The method of claim 288, wherein the autoimmune
disease or disorder is multiple sclerosis.

300. (Previously Presented) The method of claim 288, wherein the autoimmune
disease or disorder is renal transplantation.

301 . (Previously Presented) A method of treating an autoimmune disease in an
animal comprising administering a therapeutically effective amount of an anti-Neutrokine-
alpha antibody that binds to human Neutrokine alpha polypeptide having the amino acid
sequence of SEQ ID NO:2.

302. (Previously Presented) The method of claim 301, wherein the antibody is a
monoclonal antibody.

303. (Previously Presented) The method of claim 301, wherein the antibody is
recombinantly produced.

304. (Previously Presented) The method of claim 301, wherein the antibody is a
chimeric antibody.

305. (Previously Presented) The method of claim 301, wherein the antibody is a
humanized antibody.

306. (Previously Presented) The method of claim 301, wherein the antibody
comprises human constant domains.

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307. (Previously Presented) The method of claim 301, wherein the antibody is a
F(ab')2 fragment,

308. (Previously Presented) The method of claim 301 , wherein the animal is

human.

309. (Previously Presented) The method of claim 301 , further comprising detecting
the levels of B cell growth and immunoglobulin production in the animal.

310. (Cancelled)

311. (Previously Presented) The method of claim 301 , further comprising detecting
the level of B cell growth in the animal.

312. (Previously Presented) The method of claim 301 , further comprising detecting
the level of immunoglobulin production in the animal.

313. -353. (Cancelled)

354. (Previously Presented) The antibody (1 5C10) produced by the hybridoma of
ATCC Deposit Number PTA-1 158.

355. (Previously Presented) An antibody or fragment thereof that competitively
inhibits the binding of the antibody of claim 354 to the protein of SEQ ID NO: 2.

356. (Previously Presented) An antibody or fragment thereof that binds the same
epitope as the antibody of claim 354.

357. (Previously Presented) The antibody or fragment thereof of claim 356,
wherein the epitope comprises amino acid residues 227-242 of SEQ ID NO: 2.

358. (Previously Presented) The antibody or fragment thereof of claim 356,
wherein the epitope comprises amino acid residues 230-245 of SEQ ID NO: 2.

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